Different functional domains measured by cocaine self-administration under the progressive-ratio and punishment schedules in male Wistar rats

Current diagnosis of drug addiction like other mental disorders is based on clinical symptoms not on neural pathophysiology and consequently, does not provide useful information on the underlying pathophysiology and may impede the efforts to identify the underlying mechanisms. Identifying the functional deficits that are relevant to addiction and can be traced to the neural systems will greatly facilitate our understanding of the heterogeneity of the condition and improve future diagnosis and treatment. Cocaine addiction is characterized by the continued use despite the dire consequences, and the deficit in inhibitory control may play a key role in this process. This study aimed to develop a paradigm to measure the punishment-induced inhibitory regulation of reward-seeking behavior. Rats were first trained to self-administer sucrose pellets under a chained schedule and then the breaking points (BPs) under the progressive-ratio schedule, and the intensity-response effects of footshock punishment on sucrose SA were measured. Subsequently, the rats went on to self-administer intravenous cocaine, and the BPs and the punishment intensity-response effects were similarly determined. The areas under the punishment intensity-response curves (AUCs) were calculated and used as an indicator of the sensitivity of the inhibitory system. The BPs for cocaine were not correlated with the AUCs. Furthermore, the change in the BPs for cocaine induced by changing cocaine dose did not predict the change in the AUCs. The intensity-response effects of punishment can be used to measure the function or sensitivity of the inhibitory system independent of the motivational state.